The objective of this project is to continue to investigate the employment of the reticuloendothelial stimulant, glucan, as an agent for the initiation of macrophage induced destruction of malignant cells and the possible induction of tumor immunity. Studies will continue in experimental animals relative to the use of glucan systemically in order to produce generalized macrophage activation in an effort to affect disseminated tumors. The mechanisms of the macrophage mediated antitumor action of glucan will be investigated by assessment of the cytotoxic and/or cytostatic potential of glucan stimulated macrophages in vitro employing both allogeneic and syngeneic tumor cells. Studies to be undertaken relative to the delineation of the mechanism of the anti-tumor effect of glucan will be an evaluation of the influence of glucan on T and B lymphocyte function as evaluated by the response of murine spleen cells to various mitogens. Additionally, since glucan has been demonstrated to induce an enhancement in both humoral and cell mediated immunity, the ability of glucan to induce tumor immunity, as evaluated by host survival, organ function and histology will be studied in rat leukemia and mouse melanoma models. Since a problem in the employment of glucan in clinical studies is the particulate nature of glucan, studies will be conducted to produce microparticulates of glucan as well as soluble fractions. These agents will be tested for both their acute and chronic toxicity as well as their tumor inhibiting ability. These composite studies will evaluate our concept that macrohages, in their role as both monitor and killer cells, are essential in maintaining the internal environment free of malignant cells. These studies will also contribute to the potential clinical development of useful non-toxic macrophage activating agents which can be utilized in enhancing host mediated tumor cell destruction. BIBLIOGRAPHIC REFERENCES: The role of plasma recognition factors in neoplasia. N.R. Di Luzio. Trace Components of Plasma: Isolation and Clinical Significance. pp. 179-192, Am. Natl. Red Cross, Alan R. Liss, Inc., New York, 1976. Enhancement of host resistance to malignancies in experimental animals by glucan administration. N.R. Di Luzio, J.A. Cook, E.O. Hoffmann, and E. Jones. Fed. Proc. 35:311, 1976 (abstract).